Exome and genome sequencing are the predominant techniques in the diagnosis and research
of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage
is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy
number variants (CNVs). Here we compared the ability to obtain comprehensive exome
coverage for recent exome capture kits and genome sequencing techniques.We compared
three different widely used enrichment kits (Agilent SureSelect Human All Exon V5,
Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and
long-read WGS. We show that the Twist exome capture significantly improves complete
coverage and coverage uniformity across coding regions compared to other exome capture
kits. Twist performance is comparable to that of both short- and long-read whole genome
sequencing. Additionally, we show that even at a reduced average coverage of 70× there
is only minimal loss in sensitivity for SNV and CNV detection.We conclude that exome
sequencing with Twist represents a significant improvement and could be performed
at lower sequence coverage compared to other exome capture techniques.
